A meta-analysis of the association of the ACE I/D and PAI-1 4G/5G polymorphisms with recurrent pregnancy loss in Iranian women: Are the investigations adequate?

The associations of ACE I/D and PAI-1 4G/5G polymorphisms with recurrent pregnancy loss (RPL) in Iranian women have yielded controversial results. Thus, we conducted a meta-analysis to obtain more certain results. A comprehensive literature search was performed in the PubMed, Web of Sciences, Scopus, MedRxiv, SID, and CNKI databases up to January 1st, 2021, using the appropriate terms. All case-control studies were included. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to estimate the strength of associations. A total of 14 studies including eight studies with 783 patients and 761 healthy subjects on ACE I/D and six studies with 1.155 patients and 699 healthy subjects on PAI-1 4G/5G were included. Combined data revealed that ACE I/D polymorphism was significantly associated with RPL risk in Iranian women under three models i.e., allele [OR=0.744, 95% CI: (0.640-0.864); p≤0.001], dominant [OR=0.774, 95% CI: (0.601-0.996); p=0.047], and recessive [OR=0.767, 95% CI: (0.611-0.963); p=0.022]. Moreover, the pooled data showed a significant association between the PAI-1 4G/5G polymorphism and RPL risk under all five models i.e., allele [OR=2.352, 95% CI: (1.623-3.408); p≤0.001], heterozygote [OR=8.364, 95% CI: (4.744-14.756); p≤0.001), homozygote [OR=2.192, 95% CI: (1.093-4.394); p=0.027), dominant [OR=2.354, 95% CI: (1.309-4.235); p=0.004], and recessive [OR=5.208, 95% CI: (3.005-9.025); p≤0.001]. Stratification analysis revealed that these polymorphisms were associated with RPL risk by the number of miscarriages. Our pooled data indicated that ACE I/D and PAI-1 4G/5G polymorphisms were significantly associated with an increased risk of RPL in Iranian women. These significant findings showed that the investigation might be adequate for ACE I/D and PAI-1 4G/5G polymorphisms in the Iranian population.